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Study of BMF-219 in Healthy Adult Subjects and in Adult Subjects With Type 2 Diabetes Mellitus (T2D)

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ClinicalTrials.gov Identifier: NCT05731544
Recruitment Status : Recruiting
First Posted : February 16, 2023
Last Update Posted : February 13, 2024
Sponsor:
Information provided by (Responsible Party):
Biomea Fusion Inc.

Study Description
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Brief Summary:
A Phase 1/ 2 Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMF-219, an Oral Covalent Menin Inhibitor, in Healthy Adult Subjects and in Adult Subjects with Type 2 Diabetes Mellitus.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: BMF-219 Phase 1 Phase 2

Detailed Description:
This is a Phase 1/ 2 study that will examine the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple dose levels of BMF-219, an orally bioavailable selective covalent inhibitor of menin, in healthy subjects and in subjects with T2D. This study will assess the effect of BMF-219 as single ascending dose (SAD) and multiple ascending dose (MAD).
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 414 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: The subject and the investigator involved in the treatment or clinical evaluation of the subjects will be unaware of the group assignments. Specific personnel (e.g., PK assay specialist, Medical Monitor or designee, Biostatistician, Safety scientist) will be unblinded to subject treatments to permit real-time interpretation of the safety and PK data.
Primary Purpose: Treatment
Official Title: A Phase 1/2 Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, PK, and PD of BMF-219, an Oral Covalent Menin Inhibitor, in Healthy Adults and Adults With T2D
Actual Study Start Date : August 17, 2022
Estimated Primary Completion Date : July 2024
Estimated Study Completion Date : May 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Phase 1 SAD Cohorts
Phase 1 SAD Cohorts with healthy adults randomized 3:1 receiving BMF-219 or placebo.
 Drug: BMF-219
Investigational Product
Experimental: Phase 1 single dose food effect sub-study
Phase 1 single dose food effect sub-study with healthy adults randomized 1:1:1:1:1:1 receiving BMF-219 or placebo fasted, with a low-fat meal, and with a high fat meal.
 Drug: BMF-219
Investigational Product
Experimental: Phase 1 single dose tablet PK sub-study
Phase 1 single dose x3 PK tablet open-label sub-study with healthy adults randomized 1:1 receiving BMF-219 or placebo fasted, with a low-fat meal, and with a high-fat meal).
 Drug: BMF-219
Investigational Product
Experimental: Phase 2 MAD Cohorts
Phase 2 MAD Cohorts with healthy adults (MAD1) or adults with T2D (MAD 2-8) randomized 3:1 receiving BMF-219 or placebo.
 Drug: BMF-219
Investigational Product
Experimental: Phase 2 Expansion Cohort
Phase 2 Expansion Cohort adults with T2D randomized 3:1 ratio receiving BMF-219 or placebo.
 Drug: BMF-219
Investigational Product


Outcome Measures
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Primary Outcome Measures :
  1. Safety Assessments [ Time Frame: 52 weeks ]
    Assessed by treatment emergent adverse events.(TEAEs), drug discontinuation due to TEAEs, serious adverse events, clinically significant laboratory, vital, and ECG evaluations.

  2. Pharmacokinetics Assessments [ Time Frame: 12 weeks ]
    Assessed by effect of fed conditions on serial and sparse pharmacokinetic data.

  3. Change in HbA1c [ Time Frame: 12 weeks. ]
    Assess the change in HbA1c from baseline to week 12.


Secondary Outcome Measures :
  1. To determine the effects of BMF-219 on glycemic parameters in subjects with T2D. [ Time Frame: 18 months ]
    Assess changes in plasma glucose, c-peptide, and insulin at different timepoints both fasted and in response to OGTT.

  2. To determine the impact of multiple ascending doses of BMF-219 on beta-cell function in subjects with T2D. [ Time Frame: 18 months ]
    Descriptive summaries of homeostatic model assessment beta-cell function %beta and insulin resistance (HOMA-B and HOMA- IR).

  3. To assess the effect on HbA1c [ Time Frame: 12 Months ]
    Proportion of subjects achieving an HbA1c < 7% at Week 12.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Healthy Subject Inclusion Criteria:

  1. Males or females, age ≥18 and ≤65 years.
  2. BMI ≥18 and ≤35 kg/m2.
  3. Subjects are healthy on the basis of their medical history, physical examination, ECG, and routine laboratory data.
  4. Females are to be not pregnant, non-lactating. Females can be postmenopausal. Females of childbearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study.
  5. All subjects must be willing and able to provide written, signed informed consent and be willing and able to comply with all study procedures and tests.

Subjects with T2D: (MAD Cohorts) Inclusion Criteria:

  1. Males or females, age ≥18 and ≤65 years.
  2. Diagnosed with T2D within the last 15 years.
  3. Treated with lifestyle management with or without at the most 3 anti-diabetic medications with a stable dose for at least 2 months prior to screening. If on metformin, the stable dose should be at least 500mg/day.
  4. HbA1c ≥7.0% and ≤10.5%.
  5. BMI ≥25 and ≤40 kg/m2.
  6. Females are to be not pregnant, non-lactating. Females can be postmenopausal. Females of childbearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study.
  7. All Subjects must be willing and able to provide written, signed informed consent and be willing and able to comply with all study procedures and tests.

Subjects with T2D: (Expansion Cohort) Inclusion Criteria:

  1. Males or females, age ≥18 and ≤65 years.
  2. Diagnosed with T2D within the last 7 years.
  3. Treated with lifestyle management with or without at the most 3 anti-diabetic medications with a stable dose for at least 2 months prior to screening. If on metformin, the stable dose should be at least 500mg/day.
  4. HbA1c ≥7.0% and ≤10.5%.
  5. BMI ≥25 and ≤40 kg/m2.
  6. Females are to be not pregnant, non-lactating. Females can be postmenopausal. Females of childbearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study.
  7. All Subjects must be willing and able to provide written, signed informed consent and be willing and able to comply with all study procedures and tests.

Exclusion Criteria:

Healthy Subject Exclusion Criteria:

  1. Evidence or history of any clinically significant disease or malignancy.
  2. Mean QTcF ≥ 440 msec on triplicate ECGs. Use of medications known to significantly prolong the QT or QTcF interval.
  3. History of hypertension or untreated hypertension (sitting systolic blood pressure (BP) ≥140 and diastolic BP ≥90 mm Hg).
  4. Known self or family history (first-degree relative) of multiple endocrine neoplasia Type 1.
  5. History of stomach or intestinal surgery or resection (except appendectomy, hernia repair, and/or cholecystectomy).
  6. A history or evidence of human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) infection at screening or active COVID-19 infection on screening. A COVID-19 infection requiring hospitalization within the past 30 days prior to the screening visit is not allowed.
  7. Use of any live vaccines against infectious diseases within 30 days of initiation of investigational product.
  8. Current smoker of more than 5 cigarettes per day.
  9. Use of proton pump inhibitors is prohibited. Antacids are permitted but must be given a minimum of 2 hrs before or 2 hrs after administration of study drug. Subjects receiving PPIs who switch to H2receptor antagonists are eligible for enrollment in the study.
  10. Excessive use (>8 cups/day) of coffee, tea, soda.
  11. Receiving an investigational intervention or having participated in another clinical trial within 30 days.
  12. Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management.
  13. Received prior menin inhibitor treatment.

Subjects with T2D (MAD Cohorts) Exclusion Criteria:

  1. Type 1 Diabetes Mellitus or a secondary form of diabetes or any prior history of diabetic ketoacidosis.
  2. Have had recurrence (≥2 episodes) of severe hypoglycemia (defined by the occurrence of neuroglycopenic symptoms requiring the assistance of another person for recovery) within the last 6 months prior to screening or, has a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms as judged by the Investigator.
  3. Known self or family history (first-degree relative) of multiple endocrine neoplasia Type 1.
  4. Use of anti-diabetes medications (sulfonylureas, insulin, dipeptidyl peptidase-IV inhibitor [DPP-4I] [linagliptin and saxagliptin only] thiazolidinediones) within last 2 months prior to screening.
  5. Fasting plasma glucose ≥255 mg/dL.
  6. Fasting C-peptide <0.8 ng/ml.
  7. Fasting insulin >55 μIU/mL.
  8. Mean QTcF ≥450 ms. Use of medications known to significantly prolong the QT or QTc interval.
  9. Fasting triglyceride ≥500 mg/dL.
  10. Have an eGFR <60 mL/min/1.73 Equation at screening.
  11. AST ALT > 1.5 × ULN, bilirubin > 1.5 × ULN. Isolated GGT elevation >2.5 ULN without > 1.5 x ULN AST, ALT and/or total bilirubin but with a history of abnormal LFTs in the last 6 months or a medical history of a liver disorder should be excluded.
  12. History of acute or chronic pancreatitis.
  13. Serum lipase and/or amylase above 1.5 x ULN.
  14. Active hepatitis B virus (HBV) or active hepatitis C virus (HCV) at screening. Known positive test, if any, prior to screening or history of human immunodeficiency virus (HIV). An active COVID-19 infection at screening. A COVID-19 infection requiring hospitalization (or release from the hospital) within the past 30 days prior to the screening visit.
  15. Use of any live vaccines against infectious diseases within 30 days of initiation of investigational product.
  16. Subjects with positive drug screen (except marijuana [tetrahydrocannabinol (THC)] during screening.
  17. TSH >6 mIU/L or <0.4 mIU/L (on stable thyroid replacement dose for 3 months prior to screening).
  18. Severe uncontrolled treated or untreated hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg).
  19. Diagnosis of, or treatment for, any cancer within the last 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy.
  20. History of stomach or intestinal surgery or resection and/or gastroparesis (except that appendectomy, hernia repair, and/or cholecystectomy will be allowed).
  21. History of cirrhosis.
  22. Current smokers of more than 3 cigarettes per day.
  23. Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management.
  24. Use of Proton pump inhibitors is prohibited. Subjects receiving PPIs who switch to H2-receptor antagonists are eligible for enrollment in the study.
  25. History of any illness, underlying medical condition or unstable medical or psychological condition (including drug or alcohol abuse) that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering study drug to the subject.

Subjects with T2D (Expansion Cohort) Exclusion Criteria:

  1. Type 1 Diabetes Mellitus or a secondary form of diabetes.
  2. Prior history of diabetic ketoacidosis or hyperosmolar coma.
  3. History of severe hypoglycemia (defined by the occurrence of neuroglycopenic symptoms requiring the assistance of another person for recovery) within the last 6 months prior to screening or, has a history of hypoglycemia unawareness.
  4. Known self or family history (first-degree relative) of multiple endocrine neoplasia Type 1 (MEN1).
  5. Use of any of the following anti-diabetes medications within 2 months prior to screening: sulfonylureas, insulin, and the dipeptidyl peptidase-4 inhibitors (DPP4i) linagliptin and saxagliptin (sitagliptin and other DPP4i allowed) thiazolidinones [TZD]) within last 2 months prior to screening.
  6. Fasting plasma glucose ≥255 mg/dL.
  7. Fasting C-peptide <0.8 ng/ml.
  8. Fasting insulin >55 μIU/mL.
  9. Mean QTcF interval >450 ms on triplicate ECGs. Use of prescription or over-the-counter medications known to significantly prolong the QT or QTc interval is excluded.
  10. Fasting triglyceride ≥500 mg/dL.
  11. eGFR<60 mL/min/1.73.
  12. (AST) or (ALT) >1.5 × ULN, Total bilirubin >1.5 × ULN at screening.
  13. History of acute or chronic pancreatitis.
  14. Serum lipase and/or amylase above 1.5 x ULN.
  15. Active hepatitis B (HBV) or active hepatitis C virus (HCV) at screening. Known positive test or history of human immunodeficiency virus (HIV). An active COVID-19 infection at screening. A COVID-19 infection requiring hospitalization (or release from the hospital) within the past 30 days prior to the screening visit.
  16. Subjects with positive drug screen (except marijuana [tetrahydrocannabinol (THC)]) during screening.
  17. TSH >6 mIU/L or <0.4 mIU/L (on stable thyroid replacement dose for 3 months prior to screening).
  18. Severe uncontrolled treated or untreated hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg).
  19. Diagnosis of, or treatment for, any cancer within the last 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy.
  20. History of stomach or intestinal surgery or resection and/or gastroparesis.
  21. History of cirrhosis.
  22. Current smokers of more than 5 cigarettes per day.
  23. Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management.
  24. Use of Proton pump inhibitors is prohibited. Subjects receiving PPIs who switch to H2-receptor antagonists are eligible for enrollment in the study.
  25. Any known or suspected allergy to trial product, similar compounds or excipients. medical or psychological condition (including drug or alcohol abuse) or historical abnormal laboratory values that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering study drug to the subject.
Contacts and Locations
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05731544


Contacts
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Contact: Rima Sakhapara 1-844-245-0490 clinicaltrials@biomeafusion.com
Contact: Sanchita Mourya, MD 1-844-245-0490 clinicaltrials@biomeafusion.com

Locations
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Sponsors and Collaborators
Biomea Fusion Inc.
More Information
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Responsible Party: Biomea Fusion Inc.
ClinicalTrials.gov Identifier: NCT05731544    
Other Study ID Numbers: COVALENT-111
First Posted: February 16, 2023    Key Record Dates
Last Update Posted: February 13, 2024
Last Verified: February 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Biomea Fusion Inc.:
Diabetes
Type 2 Diabetes Mellitus
Healthy Volunteers
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases